Identification of single nucleotide polymorphisms (SNPs) and other genetic variants observed in receptors and post-receptor signal transducing molecules, such as heterotrimeric GTP-binding (G)-proteins, ion channels and effector enzymes, is a key first step in defining the factors that contribute to pharmacogenetic, inter-individual variation in pharmacodynamics. The principal goal is to support investigators in individual Projects and Cores through the utilization of methods to express polymorphic genes in cells and then to assess the consequence of the genetic variations on protein expression and functional activity. Investigators in Core D will approach this mission in 3 discrete steps: 1) Isolation/cloning of candidate genes and placement in appropriate expression vectors 2) Expression of wild-type and variant genes in transiently and stably transfected cells 3) Evaluation of the impact of the genetic variants on protein expression and function of the gene product. In addition, investigators in this Core will support work in projects and Cores in terms of assistance in establishing and utilizing methods to examine receptors, signaling pathways, second messengers, and electrophysiology. Dr. Brina Rana will function as Data Manager and will coordinate the exchange of data with other Projects and Cores.